The major aim of this project is to further our understanding of the nature of the malignant process in human hematopoietic neoplasms by characterizing the biological behavior of malignant cells in these disorders. Initial studies will be aimed at expanding the number of human lymphoma and leukemia cell lines presently available in order to achieve these goals. To determine possible growth requirements of human lymphoma and leukemia cells, a bank of normal adult and fetal tissue strains will be established from organs which are common sites of metastasis for these tumors. Using a quantitative clonal assay system developed in this laboratory, we will study neoplastic cells from patients with undifferentiated lymphomas, malignant histiocytosis, multiple myeloma and the myeloid leukemias for their ability to proliferate in vitro under various experimental conditions. These same neoplastic cells will be investigated for their heterotransplantability in the central nervous system of nude, athymic mice using procedures originally developed in our laboratory. Experiments of this nature will help to identify the malignant population of cells in these tumors and will enable pathological characterization of their malignant properties in an in vivo system. By use of somatic cell hybridization techniques for the production of monoclonal antibodies, immunological reagents will be developed against tumor-associated cellular antigens expressed in biopsy cells and established cell lines of histiocyte-monocyte derivation. A number of these antibodies will be studied in a preliminary manner for their clinical usefulness in the diagnosis and treatment of these highly malignant tumors and in the monitoring of tumor growth and regression in patients undergoing conventional therapy. Because of the phagocytic capabilities of these tumors, monoclonal antibodies linked to cytotoxic agents may be an unusually effective approach for serotherapy. Patients with tumors of histiocyte-monocyte derivation may therefore serve as a model system for the use of these promising new immunotherapeutic reagents.